Article
Chemistry, Physical
Nour Wasfy, Brian Doan, Faizan Rasheed, Dan Fishlock, Arturo Orellana
Summary: The mild palladium-catalyzed selective dehydrogenation of 4-alkylpyridines involves their soft enolization to generate alkylidene dihydropyridines using allyl chloroformate under metal-free conditions. The byproduct gas formation in the process makes it practical, and the reaction tolerates a broad range of functional groups while being selective for 4-alkylpyridines even in substrates with multiple pyridylic positions.
Article
Chemistry, Multidisciplinary
Finn Burg, Tomislav Rovis
Summary: A method for the internal and highly diastereoselective amino oxygenation of 1,3-dienes has been developed, catalyzed by a cationic heptamethylindenyl (Ind*) Rh(III) complex, filling the gap in the selective amino oxygenation of 1,3-dienes at the internal position.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Multidisciplinary
Yasuyuki Ura
Summary: This paper describes the challenging realization of anti-Markovnikov selectivity in Pd-catalyzed reactions, with key factors including the steric bulkiness of oxygen nucleophiles and electron-deficient cyclic alkenes as additives.
Article
Chemistry, Multidisciplinary
T. Parker Maloney, Alexander F. Dohoda, Alec C. Zhu, Forrest E. Michael
Summary: In this study, we reported a convenient and transition metal-free intermolecular propargylic C-H amination of alkynes. The reaction showed high yields for terminal, silyl, and internal alkynes with a wide range of functional groups. The regioselectivity of amination was found to be influenced by substitution pattern and relatively remote heteroatomic substituents.
Article
Chemistry, Multidisciplinary
Chuanqi Hou, Pinhong Chen, Guosheng Liu
Summary: This study reports a palladium-catalyzed Markovnikov hydroalkynylation reaction for the synthesis of branched alkynyl compounds. The reaction shows excellent functional group tolerance, high reaction yields, and good regioselectivity. Moreover, asymmetric hydroalkynylation has been achieved by introducing a chiral ligand.
CHINESE JOURNAL OF CHEMISTRY
(2023)
Article
Chemistry, Organic
Zenghui Ye, Rongjin Zhu, Feng Wang, Haobin Jiang, Fengzhi Zhang
Summary: Atom- and step-economic oxo-azidation and oxo-hydroxyphthalimidation of styrenes were developed under mild electrolytic conditions, leading to efficient synthesis of valuable alpha-azido or hydroxyphthalimide aromatic ketones from readily available starting materials. Mechanism studies revealed two different pathways involved in these transformations.
Article
Chemistry, Multidisciplinary
Kentaro Yamakawa, Kana Sakamoto, Takahiro Nishimura
Summary: In this study, enantioselective addition of an imide N-H bond to alkenes was achieved using a cationic iridium catalyst. Bulky diphosphine ligands played a crucial role in the reaction. Various substrates, such as styrene derivatives, allylsilanes, and norbornene, reacted well with alkenes to afford chiral adducts with high enantioselectivity.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Kentaro Yamakawa, Kana Sakamoto, Takahiro Nishimura
Summary: The enantioselective addition of an imide N-H bond to alkenes has been achieved using a cationic iridium catalyst. Bulky diphosphine ligands were crucial for the reaction, and various substrates including styrene derivatives, allylsilanes, and norbornene gave chiral adducts with high enantioselectivity.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Inorganic & Nuclear
Aleksa Radovic, Nikki J. Wolford, Hongze Li, William W. Brennessel, Hao Xu, Michael L. Neidig
Summary: This study focuses on the ligand effects on reactivity and in situ iron speciation in the iron-catalyzed amino-oxygenation of olefins using a bisoxazoline ligand. Experimental results reveal that the ligand and solvent have significant influence on the speciation in the precatalytic mixture, leading to the formation of different species that affect the reactivity. The in situ experiments provide evidence for the formation of an iron iminyl radical species and suggest that the functionalized hydroxylamine identity can dictate the reactivity observed in these reactions.
Article
Chemistry, Physical
Maira dos Santos Costa, Amanda de Camargo Faria, Rayssa L. Mota, Elena Gusevskaya
Summary: The study found that using green solvents as reaction media in palladium-catalyzed alkene oxidation reactions has better selectivity and faster reaction rates compared to traditional acetic acid solvents.
APPLIED CATALYSIS A-GENERAL
(2021)
Article
Multidisciplinary Sciences
Baoxin Zhang, Christoph Kubis, Robert Franke
Summary: This study reports the stable performance of unmodified cobalt carbonyl catalyst at lower syngas pressures and without phosphorus ligands at lower temperatures. The catalyst showed comparable activity to other coordinated cobalt catalysts and exhibited high regioselectivity.
Article
Chemistry, Multidisciplinary
Yue Jin, Yashi Zou, Yanhua Hu, Yunxi Han, Zhenfeng Zhang, Wanbin Zhang
Summary: A highly efficient azole-directed cobalt-catalyzed asymmetric hydrogenation of alkenes has been developed. This method allows for the synthesis of chiral pyrazole compounds with quantitative yields and excellent enantioselectivities (up to 99% ee) under mild conditions. The reaction can be conducted on a gram scale with high turnover numbers (up to 2000 TON) and has demonstrated several useful applications including the introduction of beta-chirality to drug intermediates containing an azole ring.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Organic
Alison L. Lambright, Yanyao Liu, Isaac A. Joyner, Kaitlyn M. Logan, M. Kevin Brown
Summary: The method utilizes amide-directed nickel catalysis to achieve highly selective synthesis of cyclopentane scaffolds containing boronic ester and amide functional groups. The nature of the amide directing group influences the reaction outcome, leading to predictably selective reactions based on the solvent and base counterion.
Article
Chemistry, Multidisciplinary
Yang Xi, Chenchen Wang, Qian Zhang, Jingping Qu, Yifeng Chen
Summary: This method efficiently synthesizes the chiral beta-fluoroaminated moiety with high enantioselectivity and exhibits the ability to transform the product into various vicinal benzylic fluoride derivatives with excellent stereo- and enantioselectivities.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Organic
Jiajin Zhao, Guoxiong Xu, Xue Wang, Jiren Liu, Xiang Ren, Xin Hong, Zhan Lu
Summary: A cobalt-catalyzed multipositional isomerization of conjugated dienes using an 8-oxazoline iminoquinoline ligand has been reported. This reaction is simple and efficient, yielding disubstituted 1,3-dienes with good yields and stereoselectivity.
Article
Chemistry, Multidisciplinary
Hui-Qi Ni, Phillippa Cooper, Shouliang Yang, Fen Wang, Neal Sach, Pranali G. Bedekar, Joyann S. Donaldson, Michelle Tran-Dube, Indrawan J. McAlpine, Keary M. Engle
Summary: In this study, we evaluated different ambiphilic organohalides for their participation in anti-selective carbocyclic or heterocyclic annulation with non-conjugated alkenyl amides under Pd-II/Pd-IV catalysis. By optimizing the reaction conditions, we developed protocols for the synthesis of various carbocyclic or heterocyclic compounds. We also demonstrated the reactivity of otherwise unreactive ambiphilic haloketones through Pd-II/amine co-catalysis. This method proceeds via a distinct Pd-II/Pd-IV mechanism, resulting in unique reactivity and selectivity patterns.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Zhonglin Liu, Lucas J. Oxtoby, Juntao Sun, Zi-Qi Li, Nana Kim, Geraint H. M. Davies, Keary M. Engle
Summary: The site-selective palladium-catalyzed three-component coupling of unactivated alkenyl carbonyl compounds, aryl- or alkenylboronic acids, and N-fluorobenzenesulfonimide is described in this study. Regioselectivity is enhanced by tuning the steric environment on the bidentate directing auxiliary, facilitating challenging C(sp(3))-F reductive elimination from a Pd-IV intermediate to afford 1,2-carbofluorination products in moderate to good yields.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Van T. Tran, Nana Kim, Camille Z. Rubel, Xiangyu Wu, Taeho Kang, Tanner C. Jankins, Zi-Qi Li, Matthew V. Joannou, Sloan Ayers, Milan Gembicky, Jake Bailey, Emily J. Sturgell, Brittany B. Sanchez, Jason S. Chen, Song Lin, Martin D. Eastgate, Steven R. Wisniewski, Keary M. Engle
Summary: A flurry of recent research has focused on utilizing nickel catalysis in organic synthesis. This report presents ten different bench-stable, 18-electron, formally zero-valent nickel-olefin complexes that serve as competent pre-catalysts in various reactions. Characterization and analysis shed light on the structure, bonding, and properties of these complexes, while their application in nickel-catalyzed reactions highlights the complementary nature of the different pre-catalysts within this toolkit.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Tao Zhang, Kangbao Zhong, Zhi-Keng Lin, Linbin Niu, Zi-Qi Li, Ruopeng Bai, Keary M. Engle, Yu Lan
Summary: In this study, computational evidence is presented to support the role of Zn coordination in accelerating reductive elimination from Ni(II) centers in Ni-catalyzed cross-couplings. The Zn-assisted pathway was found to have lower energy compared with direct reductive elimination from a Sigma-coordinated Ni(II) intermediate. Theoretical calculations reveal a significant Z-type Ni-Zn interaction that enhances reductive elimination.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Inorganic & Nuclear
Taeho Kang, Yue Fu, Rei Li-Matsuura, Anna L. Liu, Tanner C. Jankins, Arnold L. Rheingold, Jake B. Bailey, Milan Gembicky, Peng Liu, Keary M. Engle
Summary: A unique family of N,N,N,C-palladacycles with exceptional stability under air and moisture at room temperature were synthesized through directed 1,2-migratory insertion and fi-carbon elimination reactions. The successful isolation and characterization of these palladacycles were achieved by X-ray crystallography, NMR, and high-resolution mass spectrometry. Computational studies provided insights into the facile fi-alkyl elimination step and the high stability of these post-fi-carbon-elimination complexes.
Article
Chemistry, Multidisciplinary
Amit Kumar Simlandy, Turki M. Alturaifi, Johny M. Nguyen, Lucas J. Oxtoby, Quynh Nguyen Wong, Jason S. Chen, Peng Liu, Keary M. Engle
Summary: We report a transient directing group (TDG) strategy for site-selective palladium-catalyzed reductive Heck-type hydroalkenylation and hydroalkynylation of alkenylaldehydes using alkenyl and alkynyl bromides. This strategy allows for the construction of a stereocenter at the delta-position with respect to the aldehyde. Computational studies reveal the beneficial roles of rigid TDGs, such as L-tert-leucine, in promoting TDG binding and inducing high levels of enantioselectivity in alkene insertion.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Carla Calvo-Tusell, Zhen Liu, Kai Chen, Frances H. Arnold, Marc Garcia-Borras
Summary: We successfully engineered P411 enzymes for enantiodivergent enzymatic carbene N-H insertions through computational modeling and molecular simulations. By introducing a new H-bond anchoring point, we could control the accessible conformations of the lactone-carbene intermediate and direct the reactive carbene for an enantioselective N-nucleophilic attack. With site-saturation mutagenesis and screening, we reversed the stereoselectivity of previously engineered S-selective P411 enzymes. The resulting variant, L5_FL-B3, displayed broad substrate scope, high yields (>99%), high efficiency (up to 12,300 TTN), and good enantiocontrol (up to 7:93 er).
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Hui-Qi Ni, Malkanthi K. Karunananda, Tian Zeng, Shenghua Yang, Zhen Liu, K. N. Houk, Peng Liu, Keary M. Engle
Summary: Multistep organic synthesis allows the conversion of simple chemical feedstocks into more complex products with specific functions. This study introduces a novel approach to organic reactions that can generate multiple valuable products with different carbon skeletons in a single operation. Through a palladium-catalyzed reaction, a single alkene starting material can be converted into two structurally distinct products, demonstrating the potential for simultaneous access to diverse compounds. The findings of this study provide insights into the mechanistic details of this unique catalytic system and establish a new method for small-molecule library synthesis.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Applied
Paul J. Chirik, Keary M. Engle, Eric M. Simmons, Steven R. Wisniewski
Summary: Earth-abundant metal (EAM) catalysis has significant impact on the sustainability and cost improvement in the pharmaceutical industry. It replaces precious metals like palladium and utilizes the reactivity of first-row metals to enable more efficient routes to clinical candidates. This article describes the strategy for building these capabilities within the process group, including the development of a reaction screening platform, scalability demonstration, and increasing mechanism understanding.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2023)
Review
Chemistry, Organic
Taeho Kang, Omar Apolinar, Keary M. Engle
Summary: In this Review, the various strategies, mechanisms, and catalysts that have been applied to achieve enantioinduction in alkene 1,2-DCF are discussed.
SYNTHESIS-STUTTGART
(2023)
Article
Chemistry, Organic
Yilin Cao, Zi-Qi Li, Keary M. Engle
Summary: A nickel-catalyzed heterocycle-directed 1,2-diarylation of alkenes with aryl iodide electrophiles and arylboronic acid neopentyl ester nucleophiles is reported, resulting in a series of 1,2,4-tri(hetero)aryl products under mild conditions. The transformation is enabled by a collection of azaheterocycle directing groups, giving moderate to excellent yields. The preparative utility of the method is demonstrated by a large-scale reaction.
TETRAHEDRON LETTERS
(2023)
Article
Chemistry, Multidisciplinary
Yeongyu Hwang, Steven R. Wisniewski, Keary M. Engle
Summary: This study presents a ligand design approach for nickel-catalyzed three-component carboamidation, which is applicable to the synthesis of alkenyl amine derivatives. With this method, diverse nitrogen functionalities can be installed onto unactivated alkenes, leading to differentially substituted diamines.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Physical
Amit Kumar Simlandy, Warabhorn Rodphon, Turki M. Alturaifi, Binh Khanh Mai, Hui-Qi Ni, John A. Gurak, Peng Liu, Keary M. Engle
Summary: We report a redox-neutral catalytic coupling of nitroalkanes and unactivated alkenes that proceeds by a directed carbopalladation mechanism. The reaction is enabled by the combination of PdI2 as the precatalyst and HFIP solvent. Complex nitroalkane products, including nitro-containing carbo- and heterocycles, can be prepared under convenient conditions without the need for toxic or corrosive reagents.
Article
Chemistry, Multidisciplinary
Zi-Qi Li, Wen-Ji He, Hui-Qi Ni, Keary M. Engle
Summary: We report a regioselective, nickel-catalyzed carbosulfenylation reaction that introduces both C(sp(3)) and S(Ar)(or Se(Ar)) groups onto non-conjugated alkenyl carbonyl compounds. This reaction is compatible with alkyl/arylzinc nucleophiles and tailored N-S electrophiles, and is complementary to the previously developed 1,2-carbosulfenylation methodology that only allows C(sp(2)) nucleophiles.
